In This Edition

Gut Bacteria May Influence Metabolic Syndrome

A new study in mice supports recent findings that gut microbes
may contribute to metabolic syndrome. It also suggests that part
of the immune system plays a role in the development of metabolic
syndrome.

Common gut bacteria. Image by David
Gregory and Debbie Marshall, all rights reserved by Wellcome
Images.

Metabolic syndrome is a cluster of conditions that increases the
risk for heart disease and stroke. Doctors consider someone to
have metabolic syndrome when they have 3 or more of these risk
factors: abdominal obesity, elevated blood pressure, high triglyceride
levels, low HDL (good cholesterol) levels and diabetes or pre-diabetes.

Recent human studies suggest that gut microbial communities may
contribute to obesity and related health conditions. Microbes might
influence obesity by affecting your ability to extract energy from
food. In laboratory experiments, transferring bacteria from certain
obese mice to wild-type animals leads to increased fat in the recipient
mice. But how do different microbes wind up in different guts in
the first place? A research team led by Drs. Matam Vijay-Kumar
and Andrew T. Gewirtz at Emory University set out to investigate.
They were supported by NIH’s National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK) and the Crohn's and Colitis
Foundation of America.

The scientists did earlier work with a protein called toll-like
receptor (TLR) 5 that is highly expressed in the lining of the
intestine. TLR5 plays an important role in recognizing microbes,
activating a branch of the immune system called the innate immune
system. Mice lacking TLR5 developed colitis and gained more weight
than equivalent mice without the gene deletion. In that study,
however, the scientists didn’t ensure that all the mice began
with equivalent gut microbes. For the new study, the researchers
made sure to standardize gut microbes from the beginning by starting
with the same mouse line from the same supplier for all their experimental
and control mice.

In the advanced online edition of Science on March 4,
2010, they reported that mice lacking TLR5 grew about 20% heavier
than control mice by 20 weeks of age. The mice ate about 10% more
food and made more body fat than control mice. They also developed
several features of metabolic syndrome, including higher triglyceride
levels and cholesterol, an increase in blood pressure and insulin
resistance—a characteristic of type 2 diabetes.

All the mice gained weight when they were fed a high-fat diet
for 8 weeks, but the TLR5-deficient mice also became diabetic and
developed fatty livers. When the scientists gave TLR5-deficient
mice the same amount of food eaten by control mice, the mice didn't
become obese, yet they were still insulin resistant.

The scientists analyzed bacteria from the mouse guts and found
differences in 116 types of bacteria between the TLR5-deficient
mice and control mice. To test whether these microbes can influence
overeating and metabolic syndrome, they transplanted gut microbes
from TLR5-deficient mice into germ-free control mice. Similar to
TLR5-deficient mice, the recipient mice overate, became obese and
diabetic.

"It has been assumed that the obesity epidemic in the developed
world is driven by an increasingly sedentary lifestyle and the
abundance of low-cost high-calorie foods," Gewirtz says. "However,
our results suggest that excess caloric consumption is not only
a result of undisciplined eating but that intestinal bacteria contribute
to changes in appetite and metabolism." The next step will
be to see whether gut microbes can affect people's eating behavior
and the development of metabolic syndrome, as it does in mice.